國際毒理測試趨勢：體外微核試驗及口服急毒性與皮膚過敏性動物減量實驗

International Trends in Toxicological Testing on Experimental Animals: In Vitro Micronucleus Test, Acute Oral Toxicity Test, and Skin Sensitization Test

李彥芸(Yen-Yun Lee) ； 張敬宜(Jin-Yi Chang) ； 蔡韙任(Wei-Ren Tsai) ； 吳偉嘉(Wei-Jia Wu)

《臺灣農藥科學》 1期 (2016/12) Pp. 195-205

https://doi.org/10.6671/TPS/2016.001.11

摘要

人類藉由實驗動物的使用，促進了現今醫學、生物、農業等科學領域的發展，然實驗動物本身亦是一個生命體，當其犧牲自我貢獻出科學數據的同時，其自身的生命價值亦是值得重視的。因此有了實驗動物之保護與福祉的觀念產生，自1959 年Russell 與Burch 等(36) 科學家在其著作中提到3R 觀念時，即取代 (replacement)、減量 (reduction) 及精緻化 (refinement)，此3R 理念至今仍是動物實驗的首要圭臬與精神，進而促使國際毒理測試方法不斷更新與精進，以減少實驗動物的使用。歐洲議會更在2010 年通過新的指令 (Directive 2010/63/EU) 規定，歐盟各國主管機關必須在同意採用動物實驗時，應評估其他研究方式的可能性進行倫理評估，如需採用動物實驗時，應盡量減少動物的痛苦，以加強動物的福祉。這也就是許多國際期刊為使動物試驗精緻化，要求投稿者必須提供實驗動物管理小組 (Institutional Animal Care and UseCommittee, IACUC) 核准書、麻醉及手術過程步驟的完整敘述等資料進行審核。而本所也從2009 年開始陸續規劃與國際接軌的毒理測試趨勢，分別建立基因毒性試驗—體外哺乳動物細胞微核測試 (OECD 487)、動物減量技術口服急毒性—定比劑量致死推定法 (OECD 425 及USEPA 870.1100) 及皮膚過敏性—小鼠局部淋巴結細胞增殖分析 (OECD 442B) 等3 種試驗。目前國際間採用這些方法的實驗室已非常多，如美國的Eurofins/Product Safety Labs 與VantaBioscience、英國的Harlan Laboratories 及德國的Vivo Science GmBH 等實驗單位，適用的範圍可包含新藥開發、農藥、化學品、環衛用藥、環境污染物、醫藥品、食品、化妝品及中草藥等物質。因此，本簡報內容主要針對此3 種測試趨勢方法進行介紹。

關鍵字

基因毒性 ； 體外微核 ； 動物減量 ； 口服急毒性 ； 皮膚過敏性

並列摘要

Scientific advances in the fields of medicine, biology, and agriculture have only been possible thanks to the use of experimental animals. Although obtaining useful data can sometimes require the sacrifice of experimental animals, humans must remember that these animals are a form of life that deserve respect. As a result, concepts pertaining to the protection and welfare of experimental animals have existed as early as 1959, when Russell and Burch(36) proposed the Three Rs (i.e., 3Rs: replacement, reduction, refinement) as guiding principles for the more ethical use of animals in testing. Today, the 3Rs are accepted as standard guidelines to improve the welfare of experimental animals. To meet these guidelines, new techniques and regulations for toxicological testing have been developed. For example, in 2010, the European Union adopted Directive 2010/63/EU to regulate the protection of animals used for experimental and other scientific purposes. Specifically, this directive sought to reduce the pain and suffering of experimental animals, improve animal welfare, and encourage the consideration of alternative testing methods. Furthermore, a copy of the institutional IACUC approval document and complete descriptions of anesthesia and operation procedures are now required to publish an animal testing report. To meet international standards pertaining to animal care and use, in 2009, the Taiwan Agricultural Chemicals and Toxic Substances Research Institute (TACTRI) adopted several modern toxicological testing methods, including the In Vitro Mammalian Cell Micronucleus Test (OECD 487), the Acute Oral Toxicity: Up-and-Down Procedure (OECD 425 and USEPA 870.1100), and the Local Lymph Node Assay for Skin Sensitization (OECD 442B), which are applicable to the development of new drugs, pesticides, industrial chemicals, environmental contaminants, medicine, food, cosmetics, and Chinese herbs. These tests are comparable to those performed in international laboratories such as Eurofins/Product Safety Labs (USA), Harlan Laboratories (UK), Vanta Bioscience (USA), and Vivo Science GmBH (Germany). The purpose of this report is to briefly introduce these three toxicological testing methods.

並列關鍵字

genotoxicity ； in vitro micronucleus ； animal reduction ； acute oral toxicity ； skin sensitization